Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology

Diana Stojanovski, Olga S. Koutsopoulos, Koji Okamoto, Michael T. Ryan

Research output: Contribution to journalArticleResearchpeer-review

225 Citations (Scopus)

Abstract

Mitochondria undergo balanced fission and fusion events that enable their appropriate networking within the cell. In yeast, three factors have been identified that co-ordinate fission events at the mitochondrial outer membrane. Fis1p acts as the outer membrane receptor for recruitment of the dynamin member, Dnm1p and the WD40-repeat-containing protein Mdv1p. In mammals, the Dnm1p counterpart Drp1 has been characterized, but other components have not. Here, we report the characterization of human Fis1 (hFis1). hFis1 is inserted into the mitochondrial outer membrane via a C-terminal transmembrane domain that, along with a short basic segment, is essential for its targeting. Although expression of hFis1 does not complement the phenotype of yeast cells lacking Fis1p, overexpression of hFis1 in tissue culture cells nevertheless causes mitochondrial fragmentation and aggregation. This aggregation could be suppressed by expressing a dominant-negative Drp1 mutant (Drp1K38A). Knockdown of hFis1 in COS-7 cells using RNA interference results in mitochondrial morphology defects with notable extensions in the length of mitochondrial tubules. These results indicate that the levels of hFis1 at the mitochondrial surface influences mitochondrial fission events and hence overall mitochondrial morphology within the cell.

Original languageEnglish
Pages (from-to)1201-1210
Number of pages10
JournalJournal of Cell Science
Volume117
Issue number7
DOIs
Publication statusPublished - 1 Mar 2004
Externally publishedYes

Keywords

  • Fis1
  • Mitochondria
  • Organelle biogenesis
  • Protein import

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